Endocrinology Flashcards
Diagnostic test thresholds for diabetes diagnosis
Random plasma glucose
- PreDM 140-199
- DM 200
Fasting plasma glucose
- PreDM 100-125
- DM 126
2-hour OGTT
- PreDM 140-199
- DM 200
HgA1c
- PreDM 5.8-6.4%
- DM 6.5%
Labs to distinguish type 1 from type 2 DM
C peptide
Antibodies:
Anti-insulin antibodies (IAA)
Anti-islet cell cytoplasm antibodies (ICA)
Anti-Glutamic acid decarboxylase antibodies (GAD) -MC
Anti-tyrosine phosphatase antibodies
Precipitating factors for DKA
Undiagnosed diabetes Missed insulin doses Infection - PNA, gastroenteritis, UTI Severe medical illness - MI, stroke, bowel ischemia Trauma Medications - glucocorticoids alcohol or drug abuse Pancreatitis
DKA - features and diagnosis
Features: Weakness Polyuria and polydipsia Abdominal pain, nausea, vomiting Altered mental status -> coma Kussmaul breathing - deep, labored, fast Fruity order on breath Dry mucous membranes low skin turgor
Dx:
Glucose 200-600
High anion gap metabolic acidosis - ABG, BMP
Serum/urine ketones
Sodium +/- pseudohyponatremia
Potassium looks high - low total body K, excreted in urine
Treatment of DKA
Admit to ICU
IVF - NS or LR - large boluses - esp hypotension
IV insulin
Add IV glucose when glucose less than 200
Electrolyte management: potassium above 4, magnesium above 2, phosphorus, calcium
Identify and treat any precipitating factors
Wait until anion gap closes to stop insulin - bridge to subcutaneous insulin for maintenance
DKA vs HHS
DKA: T1DM Glucose over 200 pH less than 7.3 ketones present High anion gap Normal/variable plasma osmolality
HHS: T2DM Glucose over 600 pH >7.3 small or absent ketones normal/variable anion gap
Plasma osmolality >320 (high)
Hyperosmolar hyperglycemic non-ketotic state
Features:
Polyuria and polydipsia
Dehydration
AMS, seizures, stroke, coma
Dx:
Glucose >600-800
No acidosis
elevated plasma osmolality (>320)
Tx: Admit to ICU IV insulin Correct electrolytes Identify and treat underlying disorder
End treatment: normalized glucose and osmolality
Nonproliferative diabetic retinopathy
Cotton wool spots
Hard exudates
Microaneurysms
Tortuous vessels
Tx: if severe - panretinal photocoagulation PRP
Surveillance and blood glucose and BP control
Proliferative diabetic retinopathy
Neovascularization - fragile new vessels prone to hemorrhage Cotton wool spots Hard exudates Hemorrhage AV nicking Edema
Tx: PRP VEGF inhibitors Intravitreal corticosteroid Vitrectomy (if vitreous hemorrhage)
Diabetic nephropathy
Microalbuminemia ->
Overt proteinuria ->
Nephrotic syndrome and/or Progressive kidney dysfunction
-Kimmelstiel-Wilson nodules on pathology
-> hemodyalsis
Tx: prevention - ACE/ARB
Diabetic neuropathy
Sensory:
- Progressive stocking/glove distribution
- paresthesias, dysesthesias, or numbness
- prevention of injury and infection is paramount
Motor
- poor coordination
- weakness
Autonomic
- erectile dysfunction
- postural hypotension
- incontinence
- gastroparesis (tx erythomycin, metoclopramide)
Tx:
Gabapentin, carbamazepine, pregabalin - nerve pain
TCAs, duloxetine
Narcotics, tramadol last resort
Goal: avoid injury/infection
Complications
Charcot joints - chronic progressive arthropathy
-associated with tabes dorsalis and diabetes
DM preventive care
HbA1c q3 mo -> q6 if stable at goal
urine microalbumin:cr ratio - over 300, get 24 hr urine
lipids q1 yr
-treat with mod-high intensity over 40
Complications from bypass surgery
Deficiencies of iron, B12, folate, thiamine, vitamin D
Dumping syndrome - bloating, swelling, cramping
GERD
Vomiting
Criteria for metabolic syndrome
Abdominal obesity Elevated triglycerides Low HDL Elevated blood pressure Abnormal blood glucose
Symptoms of hypoglycemia
Adrenergic symptoms (elevated epi) Faintness Weakness Anxiousness Sweating Palpitations -beta blockers can mask the symptoms
neuroglyopenic symptoms Headache Confusion Mental status changes Seizure Loss of consciousness
Whipple’s Triad
Symptoms of hypoglycemia - especially after fasting or heavy exercise
Low plasma glucose - below 45 at time of symptoms
Relief of symptoms when the glucoses raised to normal
Reactive hypoglycemia
Excessive insulin production in response to the amount of blood glucose present
Occurs 1-3 hours after a high carb meal
Dx: mixed meals tolerance test instead of fasting to induced hypoglycemia
after gastric bypass or in prediabetes
Encourage high protein and less junk food
Insulinoma
Insulin secreting tumor are usually in the pancreas
Hypoglycemia while fasting
Get imaging CT/MRI to localize
Surgery if tumor identified
Diazoxide - inhibits insulin secretion
Octreotide
Secondary hypoglycemia to other disease
Liver disease, Malnutrition, adrenal insufficiency
Hypoglycemia during fasting
Dx: Check LFTs Markers of nutrition Cortisol stimulation test ACTH level
Alcohol induced hypoglycemia
Decreased gluconeogenesis - NADPH used up to metabolize alcohol
Hypoglycemia with fasting
Check the blood alcohol level
Give thiamine before glucose to prevent Wernicke encephalopathy
Thyrotropin releasing hormone (TRH)
Released from the hypothalamus
Stimulates TSH from pituitary
Thyroid stimulating hormone (TSH)
Released from pituitary gland
Stimulates the thyroid directly
Best test for thyroid function
Elevated in hypothyroidism
Changes exponentially with small changes in T4/T3
Thyroxine (T4)
Thyroid hormone
Replace to therapeutically in hypothyroidism
Half-life 7 to 10 days
Measure free T4 level
Low in hypothyroidism
Triiodothyronine (T3)
Thyroid hormone mostly produced in peripheral tissues
High affinity for receptor
Short half-life
Measure free T3 level
low in hypothyroidism
Thyroid binding globulin (TBG)
Protein that binds circulating T4 and T3
High in pregnancy and OCP use (high estrogen states)
Low in liver failure and nephrotic syndrome (low-protein states)
Amount of TBG affects total T4 and T3 levels, but not free levels
Thyroid peroxidase antibody (TPO)
Causative antibody (others: antithyroglobulin and antimicrosomal) in Hashimoto’s thyroiditis
Used to Determine cause of hypothyroidism
Causes of hypothyroidism
Congenital hypothyroidism Hashimoto's thyroiditis Iodine deficiency or excess Subacute granulomatous thyroiditis (de Quervain) Riedel's thyroiditis Neck radiation - including treatment for hyperthyroidism with radioactive iodine Surgical removal of the thyroid Idiopathic causes
Medications:
Amiodarone - lots of iodine
Lithium
Tyrosine kinase inhibitors (imatinib)
Clinical features and treatment for hypothyroidism
Features: Cold intolerance Weight gain Fatigue Constipation Voice hoarseness or change Menorrhagia Slowed mental or physical function Dry skin with coarse brittle hair Reflexes - slow return phase
Tx:
Levothyroxine - T4
Synthetic T3
Natural thyroid replacement - dosing inconsistencies
Hashimoto thyroiditis
Women - teens and middle age
Euthyroid state early in disease
Thyrotoxicosis d/t inflammation and destruction of follicle cells
-> painless goiter, hypothyroid
Dx:
Elevated total and LDL cholesterol - recovers as treated
Thyoid peroxidase (TPO), antithyroglobulin and antimicrosomal Abs
Tx: thyroid hormone replacement
Subacute thyroiditis
Features: PAINFUL goiter neck pain Fever Elevated ESR Low uptake on thyroid scan
Cause hyper or hypothyroidism
Tx: NSAIDS, steroids - pain replace thyroid hormone if hypo Bet-blockers if hyper continue to monitor thyroid levels
Riedel’s Thyroiditis
Young
Fixed, hard, rock like, painless thyroid
Fibrosis extends into adjacent structures
Euthyroid or hypothyroidism
Congenital hypothyroidism
Causes:
Sporadic thyroid dysgenesis
Severe iodine deficiency
Hereditary disorder of the thyroid hormone synthesis
Features: Lethargy Poor feeding Thick, protruding tongue Constipation Umbilical hernia Moderate to severe intellectual disability Maternal hormones can cross placenta - normal intrauterine development
Dx:
Newborn screen TSH
Tx: replace hormone
Causes of hyperthyroidism
Graves dz
Toxic adenoma
Toxic multinodular goiter -> obstructive sxs
Toxic adenoma
“hot nodule”
hyperfunctioning nodule takes up more iodine than surrounding tissue
single or multiple (toxic multinodular goiter)
Graves Disease
autoimmune
Stimulates TSH receptor
TSI Ab
Features:
painless goiter +/- thyroid bruits
Exophthalamos - dry eyes, abnormal EOM exam
Pre-tibial myxedema
Dx:
Low TSH - usually totally suppressed
Free elevated T4 and T3
+/- elevated TSI Ab
Thyrotoxicosis
Elevated thyroid hormone levels from thyroiditis
iatrogenic: wrong dose (accidental or intentional)
Meds with high iodine: amiodarone, IV contrast
Features: wt loss increased appetite heat intolerance sweating anxiety difficulty sleeping palpitations bowel hypermobility
Exam: tremors sinus tachycardia elevated pulse pressure warm skin hyper reflexia Afib
Long standing: CHF, Fx osteoporosis, death
Treatments for hyperthyroidism
Thionamide medications - Methimazole, propylthiouracil
Thyroidectomy
Radioactive iodine
B-blocker for sxs management
Causes of thyroiditis
Viral infection
Subacute (de Quervain, granulomatous) thyroiditis
Postpartum thyroiditis
Postpartum thyroiditis
silent
painless goiter
lower uptake on thyroid scan
Dx:
TSI Ab - rule out graves activation
Radioactive iodine - if not breast feeding
Tx: self limited, tx sxs
thyroid storm
almost always Graves disease - untreated
high mortality rate
Features: tachycardia - >140 -> sweating hyperpyrexia >103F AMS, LOC GI: N/V/D Tremor Warm, sweaty skin Goiter Eye: lid lag, proptosis, ophthalmopathy (in Graves)
Labs: low TSH, high free T4/T3
Tx:
B-blockers - control adrenergic tone
Thionamides - block synthesis/conversion
IV potassium iodide - block release of thyroid hormone
Glucocorticoids - decrease T4-> T3 conversion
ICU admit - stabilize
Once Stable -> radioactive iodine
Thyroid nodules
Extremely common
4-6% solitary cancerous
Hyper functioning nodules never malignant
Cancer risk factors: Age less than 30, >60 yo Hx of neck radiation Smoking FHx of thyroid cancer
US characteristics predictive of malignancy: Hypoechoic Irregular margins Microcalcifications Taller than wide
Management of thyroid nodule
Check TSH and thyroid US
Hyperthyroid -> radionuclide uptake and scan
- HOT nodule -> treat as hyperthyroid
- COLD nodule -> FNA
Hypothyroid or euthyroid -> +nodule go to FNA, no nodule FNA not indicated
Thyroid FNA cytology follow up
Nondiagnostic -> repeat FNA
Benigh -> surveillance
Indeterminant -> gene expression analysis vs surgery
Malignant or suspicious for malignancy -> surgery
Papillary carcinoma of thyroid
MC younger No hematogenous spread Mets to LN of neck Slow growing Excellent prognosis
Tx: Total thyroidectomy \+/- LN dissection \+/- radioactive iodine - large dose -large tumor, LN involvement
Follicular carcinoma of thyroid
slow moving, treatable
follicular structure
hematogenous spread
Tx: Total thyroidectomy \+/- LN dissection \+/- radioactive iodine - large dose -large tumor, LN involvement
Medullary carcinoma of thyroid
CA of parafollicular cells
Screen for Pheo before surgery - assoc w/ MEN II
Screen RET oncogene
Tx:
Surgery
does not respond to radioactive iodine
Follow calcitonin levels for remission
Anaplastic carcinoma of thyroid
undifferentiated older patients rock hard rapidly growing rapidly fatal
Tx:
surgical +/- radioactive iodine
-not efficiently making thyroid hormone or using iodine
Chemos used for unresectable thyroid tumors
tyrosine kinase inhibitors
Levothyroxine to decrease TSH, slow growth
Risk of thyroidectomy
hoarseness - damage recurrent laryngeal n
hypoparathyroidism and tetany
Tx - calcitriol, Ca, Mg
Parathyroid hormone activity
Increase osteoclast activity
Increase distal tubule Ca2+ reabsorption
decrease phosphate reabsorption “Phosphate Trashing Hormone”
increase 1-alpha-hydroxylase activity in kidney - 25-OH Vit D to 1,25 OH Vit D -> intestinal absorption of calcium, resorb phosphate renal prox tubule
Consequences of hypercalcemia
MC - asx
“Bones, Stones, Groans, Psych overtones”
Bones - pain, osteoporosis, Fx, osteitis fibrosa
Stones: renal stones, nephrocalcinosis
Goans - C/V/N, PUD (elevated gastrin d/t high cal), pancreatitis
Psych: lethargy, fatigue, depression, memory loss, personality change, confusion, stupor coma
Other: proximal m. weakness, keratitis, conjunctivitis, HTN, itching
Primary hyperparathyroidism
Causes:
Single adenoma (MC)
Hyperplasia (one or more gland)
Parathyroid cancer (rare)
Dx: high calcium low phosphate high or normal PTH high urine calcium \+/- elevated alk phos DEXA - decreased bone density Localize gland with US vs sestimibi
Surgical Tx:
Adenoma - remove gland, check intraoperative PTH
Hyperplasa - remove 3 1/2 glands, mark remaining with clip or transplant to forearm
Medical:
Cinacalcet - increases sensitivity of Ca-R on parathyroid, lowers PTH
Avoid thiazides (retain Ca) and lithium (raises PTH)
Hydration - polyuria from hypercalcemia -> fluid loss
Biphosphonates
minimize fall risks
Routine monitoring - serum Ca, Cr, bone density
Indications for surgical parathyroidectomy in primary hyperthyroidism
hypercalcemia sxs
serum Ca > 1.0 above upper limit of normal
Cr clearance less than 60
less than -2.5 T score at any sight - forearm thins faster
Under 50 yo
Treatment for hyperparathyroidism due to chronic renal disease
Tx hyperphosphatemia
- oral binders - calcium carbonate, calcium acetate, and/or sevelamer
- NOT citrate - binds aluminum
Prevent renal osteodystrophy
- calcitriol
- may require cinacalcet to suppress PTH secretion
hyperparathyroidism d/t chronic renal disease
PTH high due to:
- elevated FGF23 -> low alpha hydroxylase in kidney - no Vit D activation
- elevated phosphate - can’t excrete
Causes osteomalacia or renal osteodystrophy
Tx like primary
Hypoparathyroidism
Causes:
surgical parathyroidectomy
Autoimmune destruction
Hypocalcemia Sxs: tingling lips/fingers paresthesias carpal/pedal spasms Severe -> tetany, laryngeal spasm, seizures
Chvostek’s sign - check
Trousseau’s sign
Dx:
Low Ca, low PTH
High phosphate
High bone density - but more fx d/t abnormal architecture
Tx:
calcitriol, 1-25 OH D3
Pseudohypoparathyroidism
Tissue non-repsonsive to PTH at receptor level
AD - GNAS-1 gene mutation
- maternal imprinting
- Mom gene -> full disease - Albright’s + hypocalcemia
- Dad gene -> partial disease - Albrights with no hypocalcemia
Albright's hereditary osteodystrophy (AHO) Short stature Short 4th metacarpal developmental delay obesity
Dx:
Low Ca
High PTH
High phosphate
Tx: Calcium/Vit D supplementation
Drugs linked to hyperprolactinemia
phenothiazines - Risperidone, Haloperidol
Methyldopa
Verapamil
Treatment of prolactinoma
1st: DA agonist - cabergoline > bromocriptine
If fail -> transphenoidal surgery
If large, radiation after surgical debulking
Acromegaly
average onset to dx is 12 yrs
Features:
enlargement of jaw (teeth spread apart), nose, frontal bones (coarse facial features), hands/feet (increase in ring, glove, shoe size)
Soft tissue growth - voice deepens, macroglossia (teeth indentations in tongue), carpal tunnel syndrome, other entrapment syndromes, hypertrophy of synovial tissue and cartilage _. arthropathy, spinal cord compression if vertebrae involved
CV: HTN, LVH, diastolic dysfunction
Glucose intolerance -> DM
Increased organ size - spleen, liver, kidneys
Vision loss d/t optic chiasm compression from tumor
Tests:
IGF-1
Confirm with oral glucose suppression test
-75 g glucose -> measure GH at 1 hr and 2 hrs -> GH concentration >1 ng/mL = acromegaly
Positive test -> pituitary MRI - mass or empty sella
Tx:
Transsphenoidal resection or external beam radiation
Octreotide or lanreotide - inhibits GH secretion
If somatostatin analog fails -> cabergoline (Bromocriptine less effective)
If cabergoline fails -> pegvisomant (GH receptor antagonist)
Follow IGF 1 level
Adrenal cortex
Glomerulosa - mineralocorticoids - aldosterone
Fasciculata - glucocorticoids - cortisol
Reticularis - androgens (testosterone, DHEA-S)
Causes of Cushing syndrome
High ACTH:
- pituitary adenoma producing ACTH (Cushing disease)
- Ectopic production of ACTH (small cell lung cancer, carcinoid tumor)
Low ACTH:
Exogenous steroid medications (MC)
Adrenal adenoma or hyperplasia
Cushing syndrome symptoms
“BAM CUSHINGOID”
Buffalo hump Amenorrhea Moon facies Clots (thrombotic), Cardiac disease, Crazy (psychosis, agitation) Ulcers (peptic) Skin (striae, acne, easy bruising) Hypertension, Hypokalemia, Hirsuitism Infection Necrosis of the femoral head Glaucoma and cataracts (eye problems) Osteoporosis Immune suppression Diabetes
Long term complications of Cushing Syndrome
thormboembolic disease CV disease - mortality cause HTN, electroylte abnormalities Infection risk osteoporosis Avascular necrosis of hip DM - hard to control
Diagnostic evaluation of Cushing syndrome
Measure ACTH->
-Low - ACTH independent Cushings-> adrenal imaging
-Intermediate (normal) - get CRH test
no response -> adrenal imaging
elevated ACTH and cortisol -> ACTH dependent Cushings
-High - ACTH dependent Cushings -> pituitary MRI
Tumor - Inferior petrosal sinus sampling (IPSS) for lateralization/confirmation
No tumor - IPSS for central vs peripheral
-Central levels higher - pituitary source
-Central levels same as peripheral -> Body scan for ectopic source OR High dose dexamethasone test or CRH test
High dose dexamethasone
- if suppresses ACHT/Cortisol - likely pituitary source, “woke up” feedback loop
- if no suppression then ectopic source
Treatment of cushing syndrome
Limit exogenous steroids
If tumor - remove
-consider repeat surgery if initial surgery unsuccessful
Pituitary source - radiation to sella if surgery not possible
Mifepristone - blocks cortisol receptors for refractory or inoperable Cushing syndrome with hyperglycemia
Ectopic - treat underlying disease
Triad of hyperaldosteronism
Hypertension
hypokalemia
metabolic alkalosis
Primary Hyperaldosteronism (Conn syndrome)
Aldosterone:
Renin:
Aldosterone/Renin:
Cause
Treatment
Aldosterone: high
Renin: low
Aldosterone/Renin: high
Cause:
Adrenal adenoma
Bilateral hyperplasia
Treatment:
Remove adenoma OR spironolactone
Secondary hyperaldosteronism
Aldosterone:
Renin:
Aldosterone/Renin:
Cause
Treatment
Aldosterone: high
Renin: high
Aldosterone/Renin: low
Cause: Renal artery stenosis CHF Nephrotic syndrome Cirrhosis (Kidney senses low BP/hypoperfusion)
Treatment:
Treat underlying cause OR spironolactone
Non-aldosterone mineralocorticoid hyperaldosteronism
Aldosterone:
Renin:
Aldosterone/Renin:
Cause
Treatment
Aldosterone: low
Renin: low
Aldosterone/Renin: low
Cause:
Cushing syndrome
Licorice ingestion ( enzyme blocks conversion of cortisol -> cortisone; aldosterone receptors stimulated)
Treatment:
Treat Cushing syndrome
STOP EATING LICORICE!
Primary adrenal insufficiency (Addison’s dz)
Affected gland: Causes: ACTH: Glucocorticoid deficiency: Mineralocorticoid deficiency:
Affected gland: adrenal cortex
Causes:
Autoimmune (MC)
Infection (TB)
Hemorrhage
ACTH: very high
Glucocorticoid deficiency: yes
Mineralocorticoid deficiency: yes
(no rise of cortisol with cosyntropin (ACTH analog) stim test)
Secondary adrenal insufficiency
Affected gland: Causes: ACTH: Glucocorticoid deficiency: Mineralocorticoid deficiency:
Affected gland: pituitary (pan-hypo)
Causes: Surgery Tumor Hemorrhage Autoimmune
ACTH: low
Glucocorticoid deficiency: yes
Mineralocorticoid deficiency: no
Tertiary adrenal insufficiency
Affected gland: Causes: ACTH: Glucocorticoid deficiency: Mineralocorticoid deficiency:
Affected gland: Hypothalamus (lack CRH)
Causes:
Exogenous steroid administration
ACTH: low
Glucocorticoid deficiency: yes
Mineralocorticoid deficiency: no
Labs and treatment for adrenal insufficiency
low Na high K eosinophilia low cortisol high ACTH (primary) Low ACTH (secondary and tertiary)
Tx:
Treat underlying disease
glucocorticoids: hydrocortisone, dexamethasone, prednisone
Mineralocorticoids - Addison’s: Fludrocortisone
-need more cortisol during stress
Adrenal (Addisonian) crisis
S/s: shock severe weakness Fever AMS Vascular collapse
Acute onset adrenal insufficiency (infarction or acute b/l adrenal hemorrhage)
Tx:
Fludrocortisone with high dose hydrocortisone (IV)
Electrolyte management - potassium drops fast with fludrocortisone replacement, high sodium
IVF if hypotensive
IV glucose
Vasopressors if needed for shock
11 B hydroxylase deficiency
high androgens -> virilization of girls
High DOC -> HTN
17 alpha hydroxylase deficiency
only aldosterone -> very very high levels HTN Ambiguous genitalia in boys Amenorrhea later in girls high Na, low androgens
21 alpha-hydroxylase
mineralocorticoid deficiency -> hypotension, low Na, high K - salt wasting
High androgens -> virilization and ambiguous genitalia in girls
Pheochromocytoma
Episodic Palpitations with episodic tachycardia CP Diaphoresis with pallor Headach Anxiety Episodic (labile) BP
Dx:
24 hr urine catecholamines - metanephrine, normetanephrin, VMA
Tx:
resect - pretreat with alpha blocker - phenoxybenzamine or phentolamine; then beta blocker
Can use carvedilol or labetalol
MEN syndromes
MEN1 (PPP):
Parathyroid
Pituitary
Pancrease
MEN2a (PPM):
Parathyroid
Pheo
Medullary thyroid cancer
MEN2b (PMM):
Pheo
Medullary thyroid cancer
Mucosal neuromas
MEN2: RET
